This invention is concerned with platforms, devices and methods useful for analytical assays in fluid samples. It is especially concerned with determining the presence of one or more analytes in small volumes of whole blood, although it is not so limited.
Many immunoassay procedures have now been developed which utilize reactions taking place on dry porous carriers such as nitrocellulose membranes through which samples to be analyzed flow by capillary action, the reaction products being detectable either visually or with an instrument such as a reflectometer or fluorometer. While not so limited, these procedures often involve antigen/antibody reactions in which one member of the reactive pair is labeled with a detectable label. Typically, the label is an enzyme label or a particulate direct label, for instance sol labels such as gold. The art is well aware of many useful labels and their methods of operation.
Typical immunochromatographic devices of this nature are described in several United States and foreign patents including U.S. Pat. Nos. 4,703,017; 4,774,192; 4,839,297; 4,861,711; 4,960,691; 5,075,078; 5,110,724; 5,120,643; 5,135,716; 5,591,645; 5,622,871; 5,654,162; 5,656,503; 5,714,389; 5,989,921; 6,020,147; 6,156,271; 6,171,870; 6,187,598; 6,214,629; 6,228,660; 6,319,676; 6,352,862; 6,410,341; 6,485,982; and 6,534,320.
These patents generally describe devices that are composed of two basic parts: a dry porous carrier through which a fluid moves by capillary action and reactions determinative of the analyte take place; a casing formed with sample application means that supports the dry porous carrier and may contain a window to facilitate viewing of the results. Sample volume is typically measured before it is applied to the dry porous carrier.
These representative devices have permitted major diagnostic advances in the medical and veterinarian fields. However, some of them are deficient because they are expensive to manufacture, not easy to use or do not perform with the desired speed. None of them have proved capable of performing an immunoassay on small volume samples typically obtainable from a finger puncture without adding extra solution. The devices of this invention alleviate those problems because they are easy to manufacture and even in the hands of a novice or unskilled personnel will provide the required information rapidly and efficiently utilizing as little as one drop of sample. The devices of this invention also incorporate mechanisms to ensure that a minimum sample volume is present before test begins and the minimum sample volume is maintained during the testing process.
The products and procedures of this invention and their disclosed modifications can be utilized for many diagnostic purposes as well as for following the course of mammalian diseases and therapeutic treatments. A particular advantage is that the products and methods are applicable to small volumes of whole blood such as can be obtained from a simple finger puncture. The invention is applicable to substantially any field in which a ligand or analyte is detected or quantified by antigen/antibody or equivalent reactions.
Analytes which may be detected in accordance with this invention include, for example, those indicative of pregnancy, ovulation, cancers such as prostate cancer and cardiovascular events. The analytes include for example hCG (human chorionic gonaditropin), LH (luteinizing hormones), PSA (protein specific antigen), myoglobin, troponins, and creatinine kinase MB.
Additional applications of the invention include recognition of analytes associated with viral infections such as hepatitis and bacterial infections such as Helicobacter pylori responsible for gastrointestinal ulcers as well as infections caused by Salmonella genus and such gram positive bacteria as Bacillus anthracis S. pyrogenes, S. pneumoniae and E. faecalis. 
As the description of the invention proceeds, it will be apparent that in addition to its utility for the assay of small sample volumes, another very important advantage is its applicability to immunoassay and non-immunoassay formats requiring the separation of red blood cells from plasma through fluid pathways.
The facility with which the devices may be employed makes it possible for their use by untrained personnel at home or in a doctor's office as well as for rapid determinations in an ambulance, emergency room, urgent care centre and laboratory.